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Benchwork in the age of open science

Jul 25, 2012 – jeff

What does our new age of open science and open data mean for research that’s mainly laboratory benchwork? Most of the major ecology & evolution journals now require that the data for papers also be published in an open-access repository like GenBank (for nucleotide sequences), Treebase (for phylogenetics), and Dryad (for other kinds of data). In at-the-bench wet-lab research, there’s often a fair amount of analysis linking the raw observations, the statistical result, and its biological interpretation. How much of that process should go into a public repository, and in what form?

In my own field of microbial evolution, one way in which I’d find open data useful has to do with fitness. There are many different ways to measure the survival and reproductive success of organisms, and they each have their uses. I’ve found when reading papers that there are often times in the authors plot their fitness data in one way, and I wonder what it’d look like plotted another way. For example, I often see papers that plots mean group productivity and within-group relative fitness (a multilevel selection partition of social evolution), and I wonder what the data would look as the absolute fitness for each microbial genotype (the neighbor-modulated fitness partition in kin selection theory). Much of the kin selection/group selection debate is about the best way to calculate and think about fitness. I prefer to plot fitness data in a way that’s easily interpreted multiple ways. But it’d be nice to at least grab other people’s data so I can replot it a bit. So here’s my recommendation:

Make sure that the data you archive includes the raw colony counts (or plaque counts, or cell counts). With that, anybody can easily calculate their favored fitness measure.

I’ve been working on a project that involves a large amount of flow cytometry data. How much of my data and calculations should go into Dryad? I’m tempted to say: all of it. From the raw data files, to the flow cytometry gating scripts, to the cell counts to the derived values (growth rates, fitness, etc), to the statistical analyses, to the scripts for making the figures. Why not?

Sharing everything also helps us become better scientists. I often learn a few things when I look at other peoples’ scripts and spreadsheets. I’ve traditionally used Excel for basic data manipulation and plotting. Now, though, I’m thinking that maybe I should try to do as much as possible in R—the scripts are easy to share, it’s easier to use for for large data sets, and it avoids the copy/paste errors that sometimes crop up in spreadsheets.

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Comment 1

    How to write a paper people will cite

    Jul 13, 2012 – jeff

    Here’s some great tips for writing scientific papers from Steve Ellner (link to original pdf). Ellner presents them as tips for theoretical papers, but I think they’re good practice for any paper:

    1. Don’t maintain suspense.

    • Present the topic clearly at the very beginning.
    • Explain the relevance of the paper at the very beginning.
    • Quickly telegraph where the entire paper will be going. Give away all your punchlines in the abstract, and do it again in the Introduction.

    2. Make the paper easy to skim.

    • Make sure that the “meat”—the core that everyone should read—is well labeled and easy to find.
    • Explain your main results using graphs.
    • Remove from the main text any technical details that aren’t needed for the flow of ideas. Readers shouldn’t have to stop and think about whether or not they have to think about an equation.
    • Use signposting to help people “peel the onion”—get as deep into the paper as they want, but no deeper. Technical sections should be prefaced by an explanation of what and who it’s for, so it’s easy for a reader to tell if they should read it, skim it, or skip it for now.
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    Comment 1

      Fictitious science

      Jun 14, 2012 – jeff

      One of the drawbacks to being a scientist is that science fiction becomes harder to enjoy. Storytelling requires a certain suspension of disbelief to work. But when your day-to-day job involves asking questions about how the natural world works, sci-fi movies are full of things that take you out of the story and leave you saying “Oh, come on“. I’ve been reminded of this after seeing Ridley Scott’s film Prometheus, a prequel to his deservedly classic Alien. Some of the things I found myself thinking during the movie:

      • If the aliens seeded life on earth with DNA oligomers (PCR primers, basically) like this computer animation is showing us, why did they have to sacrifice one of themselves to do it? Wouldn’t it be easier to just chemically synthesize them the way we do?
      • If this is supposed to be the origins of life on earth, then why is it showing us metazoan zygotes? And didn’t they just show us a landscape full of plants, anyway?
      • Why aren’t any of these characters saying anything about how wierd it is for a rocky moon to have an atmosphere full of oxygen?
      • If this is a barren moon, then why are there earthworms? And why are the earthworms sometimes meal worms (plant-eating insect larvae)?
      • Why don’t any of these people act like real scientists, or at least like professionals?
      • Why is this movie rehashing trite 1950′s cliches about the difference between humans and robots being emotion and curiosity after just showing us the android character having feelings and being curious?
      • If the aliens engineered life on earth, then doesn’t making it look like a species of primate evolved to have the same genome as them seem wierdly narcissistic?
      • How did that alien get so big so fast without eating anything?

      It’s okay for movies to leave things unexplained. I’m cool with that. Scientists live in a world full of unexplained things. I’d even prefer that movies to leave things unexplained and just chalk it up to alien technology or whatever. Their explanations are usually boring and stupid, anyway. But when the plot revolves around events that any undergrad biology major could poke holes in, well, it’s hard to get past that. Prometheus apparently did have a science consultant, though his involvement seems to have been limited a single conversation. Film makers hire people whose whole job it is to make sure that continuity of appearance is maintained from shot to shot. Can’t they hire someone to make sure the science makes sense, too? Or at least isn’t unnecessarily egregious? Please?

      I don't understand, therefore aliens (and/or God)

      The worst part of Prometheus for me, though, is that the movie is anti-science without even realizing it. Like, for example, the part where the main protagonist couple (archaeologists) claim that aliens engineered life on earth. One of the other characters reasonably asks what evidence they have for this, and the main protagonist says “It’s what I choose to believe”. Ugh. The movie presents this as a heroic act rather than, you know, pants-on-head retarded. To be clear here, this is the equivalent of a professional archaeologist saying that aliens built the pyramids of Egypt. The only response other characters have to this conspiracy idiocy is to whine that it goes against “Darwinism”—as if evolutionary biology were a philosophical belief rather than, you know, science supported by observable facts. In spite of this, the filmmakers inexplicably believe that one of their protagonists is a skeptic.

      Dear Mr. Scott: Richard Feynman was right when he said “Science is a long history of learning how not to fool ourselves.” What you show us is self-deception of the worst kind.

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      Comment 5

        Don’t bury the lead

        Jun 1, 2012 – jeff

        The conference I was at last week included a session in which each poster presenter was given a one-slide, 60-second slot—a movie trailer for their poster, you might say. It’s an interesting approach, though I’m still unsure whether I like it or not. One thing that really struck me was that the vast majority of presenters never even stated what their main finding was. Most of them were like, “Here’s the general topic of my poster and the organism I study. If you want to hear more, come by my poster.” I found it frustrating as both as a potential poster viewer and as someone who believes in taking scientific communication seriously. So please, poster presenters and papers writers of the world:

        Scientists already struggle with a deluge of more papers, posters, and talks than they could ever feasibly process. Give them reason to believe their time and attention will be well-spent on yours.

        Also, the whole “if you want to hear more, come by my poster” bit is just wasted time and breath. Advertisements for toothpaste don’t bother saying “Buy FluoroWhite Tooth Creme if you want teeth like this!” because they know their viewers already recognize the ad for what it is—an ad.

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        Comment 3

          Setting the right tone

          Mar 22, 2012 – jeff

          I’ve been finding that the problems reviewers sometimes have with my papers is not so much the actual experiments or the conclusions drawn from them, but rather the tone with which they are presented. Take this passage from a paper we’re revising:

          To avoid telling “just-so stories”, researchers studying adaptation should actively identify, test, and exclude alternative hypotheses. As George Williams famously put it, “adaptation is a special and onerous concept that should not be used unnecessarily, and an effect should not be called a function unless it is clearly produced by design and not by chance”. Selection is an important mechanism of evolution, but not the only one. Nonadaptive mechanisms like mutation and drift can also play important roles. Mechanisms by which individuals may directly benefit from expressing a trait should also be explored.

          This passage seems to evoke strong emotional responses from some people (and not because of the awkward passive voice at the end). I thought we were just describing good scientific practice for studying adaptation. The reviewers apparently thought it was patronizing. One reader even thought that using the phrase “just-so stories”, automatically counted as a full endorsement of Steven J. Gould & Dick Lewontin’s attack on behavioral ecology. The passage seems to make some people really defensive, so I think for the sake of the paper we’re going to take it out. Which is too bad, since I think it’s a message that some researchers could stand to hear (or hear again).

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          Comment 1

            Gut inflammation can boost horizontal gene transfer between pathogenic and commensal Enterobacteriaceae

            Feb 18, 2012 – jeff

            Plasmids are mobile bits of DNA that play a key role in bacterial evolution. They shuttle genes for things like antibiotic resistance and pathogen virulence among different strains or species of bacteria. But not all plasmids carry these genes, and it’s been an outstanding question how plasmids persist in bacterial populations. One possibility is that they’re a kind of genetic parasite, slightly reducing the fitness of the cells they infect but continually infecting new bacteria. One problem with this idea, though, is that their infection rates often don’t seem high enough for a purely parasitic lifestyle.

            A new paper by Bärbel Stecher and colleagues at ETH Zürich shows that when Salmonella infect mammalian guts they create an environment that drastically increases plasmid transfer among the bacteria there. They inflame the gut tissue, causing a “bloom” of resident E. coli. All those bacteria bump into each other more, allowing plasmids—which spread by direct contact between bacterial cells—to go gangbusters. The paper has a lot of good experiments showing that it’s the increased bacterial density, and not the inflammation, that causes increased plasmid transfer.

            The implication is that plasmids can make a living as parasites if Salmonella and other pathogens cause enough gastrointestinal disturbance, as they might in the developing world or in nonhuman mammal populations. I did find overblown the authors’ claims that their findings “shift the current paradigm” because they show that Salmonella and E. coli share plasmids (which we already knew) and “boost” pathogen evolution (which their findings do not show), but overall this is a pretty cool paper.

            Stecher B, Denzler R, Maier L, Bernet F, Sanders MJ, Pickard DJ, Barthel M, Westendorf AM, Krogfelt KA, Walker AW, Ackermann M, Dobrindt U, Thomson NR & Hardt W-D (2012) Gut inflammation can boost horizontal gene transfer between pathogenic and commensal Enterobacteriaceae. PNAS 109: 1269-1274.

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              What makes something “systems biology”?

              Feb 10, 2012 – jeff

              Like many biologists, I’ve wondered at times what the relatively new discipline of systems biology is all about. A lot of things get called systems biology, from genomics to metabolism to gene regulation. I often find the systems biology approaches to these fields pretty interesting, even when it’s fairly removed from my research area. Like myself, systems biologists often have a background in physics. Sometimes systems biology even includes microbial cooperation. So what ties it all together?

              Well, systems biology:

              • studies dynamic, complex systems whose behavior is governed by the interactions of their component parts
              • uses quantitative, data-rich measurements of dynamical behavior
              • uses mathematical and computational models to predict and analyze dynamical behavior

              Viewed this way, I would argue that systems biology has a lot in common with ecology and evolutionary biology. In some ways, it’s just population biology applied to molecules and cells rather than individuals and species. Asking how genetic regulatory circuits create persistent cycles of gene expression rather than coming to some stable equilibrium is not all that different than asking how predator/prey dynamics create population cycles rather than coming to some stable equilibrium. And with any luck, systems biology will help bridge the traditional divide between population biologists and their more mechanistic colleagues.

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                Tragedy of the commons among antibiotic resistance plasmids

                Jan 10, 2012 – jeff

                smith (2012) Tragedy of the commons among antibiotic resistance plasmids. Evolution. doi: 10.1111/j.1558-5646.2011.01531.x | Early view at Evolution

                Abstract: As social interactions are increasingly recognized as important determinants of microbial fitness, sociobiology is being enlisted to better understand the evolution of clinically relevant microbes and, potentially, to influence their evolution to aid human health. Of special interest are situations in which there exists a “tragedy of the commons,” where natural selection leads to a net reduction in fitness for all members of a population. Here, I demonstrate the existence of a tragedy of the commons among antibiotic resistance plasmids of bacteria. In serial transfer culture, plasmids evolved a greater ability to superinfect already-infected bacteria, increasing plasmid fitness when evolved genotypes were rare. Evolved plasmids, however, fell victim to their own success, reducing the density of their bacterial hosts when they became common and suffering reduced fitness through vertical transmission. Social interactions can thus be an important determinant of evolution for the molecular endosymbionts of bacteria. These results also identify an avenue of evolution that reduces proliferation of both antibiotic resistance genes and their bacterial hosts.

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                  “A whole dimension of completely weird, incredible things”

                  Nov 28, 2011 – jeff

                  Errol Morris has this “Op-Doc” (Opinion-Documentary, as odd as that sounds) over at the New York Times. Technically, it’s about historical research, but I think the phenomenon holds true for biology, as well. As interviewee Tink Thompson puts it, “if you put any event under the microscope, you will find a whole dimension of completely weird, incredible things going on”. I’ve always loved Morris’ work. A lot of it deals with issues of knowing—how we know what we know, how we sometimes deceive ourselves, what evidence does or doesn’t say. Important issues for any scientist.

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                    Contagion

                    Nov 19, 2011 – jeff

                    Scene from ContagionI finally got around to seeing the film Contagion, a realistic portrayal of what a serious viral pandemic would look like in our day and age. Unlike the vast majority of outbreak films, Contagion gets a lot of the science right. The basic reproductive number R0, for example, makes an appearance in the film. The film’s fictional MEV-1 virus was inspired by Nipahvirus. MEV-1 has an R0 of 2-4 and a mortality rate of ~25% — severe, but realistic. Epidemiologist Ian Lipkin consulted on the film.

                    My favorite line is when the military asks CDC Deputy Director Lawrence Fishburne if the virus was a bioterrorist attack, like a weaponized bird flu. Fishburne reponds, “No one has to weaponize the bird flu. The birds are doing that.”

                    The only part I really disliked about the film is how the virus is described as “mutating” or “changing”, but never “evolving”. Unfortunately, this aspect is also a realistic description of our public health system.

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                    Comment 4

                      Work and labor

                      Oct 18, 2011 – jeff

                      One of the things that seems wierd to me about science as a profession is how the job often requires both esoteric activities like probability theory or genetic engineering and mundane menial labor like washing dishes or mixing large amounts of dirt. As a graduate student I used to want to do everything in the lab myself: making media, counting plates, all of it. Part of it was that I wanted to know how every part of my experiments worked, and part of it was perfectionism and paranoia. Now, I find myself wanting to teach someone how to do that stuff well, and have them do the tedious work for me. Especially the part where you’ve already done the pilot experiments and the first replicate so you already know what the answer’s going to be — you’re just getting clean data for the paper. Now, I’d rather develop the assays, get them working reliably, and then let someone else finish out the data collection.

                      I have to say, though: my experience of lab work has recently been completely transformed since purchasing an mp3 player (I’m a slow adopter). Before, it was like, “I need to make media? Again? Grumble grumble…” Now it’s like, “Aw, hell yeah”.

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                        Slime molds get their 15 minutes

                        Oct 10, 2011 – jeff
                        Slime molds

                        Photo: Steven L. Stephenson

                        Dictyostelium and its relatives are getting some time in the limelight from Carl Zimmer in the New York Times. The article even includes some coverage of our lab’s work on the evolution of cooperation.

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                          University of Houston visit

                          Sep 26, 2011 – jeff

                          Last week I had the opportunity to visit the University of Houston. When our lab was still at Rice I went to a talk or two at UH but never really got much chance to interact with the research groups there. So it was great fun to talk evolutionary genetics with Tim Cooper and his lab, social amoebae with Elizabeth Ostrowski, evolutionary networks with Ricardo Azevedo, behavior and morphology with Tony Frankino, ant behavior with Blaine Cole, and food and art with Dan Graur (over dinner).

                          The audience for my talk was mostly biologists, not necessarily in my field of study, many of whom may not have been ecologists or evolutionary biologists. So I used the opportunity to develop what will hopefully become my job talk. I’ve been inspired by Will Ratcliff’s “Morgan Freeman” philosophy for scientific talks. The idea is that it should be a story, presented with engaging images, and it’s your job to guide the audience through that story with an easy-to-understand narrative.

                          One thing I’ve learned: making slides is no substitute for actually practicing a talk. Even if you mentally run through your narrative as you make slides, when you actually get to talking you’ll inevitably discover places where the narrative isn’t as clear as you thought it was.

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                            Distinguishing causes of virulence evolution

                            Sep 2, 2011 – jeff

                            smith j (2011) Distinguishing causes of virulence evolution: Reply to Alizon and Michalakis. Evolution In press. doi:10.1111/j.1558-5646.2011.01428.x | Journal

                            Abstract: In a recent study of the symbiosis between bacteria and plasmids, the available evidence suggests that experimental evolution of plasmid virulence was primarily driven by within-host competition caused by superinfection. The data do not exclude the possibility, however, that a trade-off between virulence and infectious transmission to uninfected bacteria also played a minor role.

                            This one’s an in-print discussion between Samuel Alizon, Yannis Michalakis, and myself. They were worried that some researchers might interpret my earlier paper about plasmid evolution as rejecting the hypothesis that pathogen virulence can be influenced by a trade-off between infectious transmission and virulence. So they made some mathematical models to determine what kinds of evidence we’d need to really rule out the influence of such a trade-off. The work I did doesn’t rule out a trade-off, but it does show that competition among pathogens within hosts was necessary and sufficient to explain how plasmid virulence evolved.

                            I found it nice (and useful) to talk with the authors before we sent in our respective manuscripts. It helped clear up some places where we were using language in a way that could be misinterpreted and to focus on places where there might be real issues. In the end, my impression is that we basically agree about what my paper does and doesn’t show, but they wanted to use it as a sounding board for how we should go about testing virulence theory.

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                              Science as it really happens

                              Aug 4, 2011 – jeff

                              Electron cafe made this wonderful diagram showing the scientific process as it appears on movies and TV versus the scientific process as actual scientists experience it day-to-day:

                              Science: perception and reality

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